Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this work comprehensive data of antioxidant enzymes are reviewed and their role in carcinogenesis is discussed. When compared to their normal tissue counterparts, more of the tumor tissues were low in Cu, Zn-SOD and catalase activity and in some cases in Mn-SOD. It is probably characteristic for tumor tissues. Glutathione peroxidase, and glutathione reductase and glucose-6-phosphate dehydrogenase activities are highly variable. The reason why cancerous cells exhibit abnormal levels and activities of antioxidant enzymes is unknown. It was hypothesized, that during formation of the tumor, by certain obscure mechanism, cells with imbalance of antioxidant enzymes profile were selected over normal cells. It is not known whether the changes in antioxidant defence observed in cancerous tissues play a role in carcinogenesis, or are formed as a results of the disease.
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PMID:[Activity of antioxidant enzymes in cancer diseases]. 763 95

In the present paper we report the production of a monoclonal antibody against rat MnSOD, a supposed tumor-suppressor protein, using a purified synthetic peptide encompassing amino acids 184-198 to immunize mice, without conjugation to a carrier. The resulting antibody is able to recognize the native form of the protein, since it can immunoprecipitate the MnSOD activity in rat liver homogenate. In Western blot studies, the antibody recognizes a protein of 24 KD M(r), whose concentration varies according to the MnSOD activity and it apparently recognizes also human and mouse MnSODs. The protocol of immunization gives high yield of secreting lines. This monoclonal antibody will allow the detection of structural and functional alterations of MnSOD.
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PMID:Preparation of a monoclonal antibody against rat MnSOD, using a COOH-terminal peptide. 769 May 59

Tumor necrosis factor-alpha (TNF) is a multifunctional cytokine which is cytotoxic for some tumor cells and transformed cells. The molecular mechanisms which render transformed and tumor cells sensitive to the cytotoxic action of TNF are unclear. We show here that an increased expression of the c-Myc oncoprotein strongly increases cellular sensitivity to TNF cytotoxicity. In Rat1A fibroblasts, which are resistant to TNF, the addition of TNF with a concomitant activation of a hormone-inducible c-Myc-estrogen receptor chimera (MycER) resulted in apoptotic cell death. Similarly, c-Myc overexpression enhanced the sensitivity of NIH3T3 fibroblasts to TNF-induced death. The c-Myc and TNF-induced apoptosis was inhibited by ectopic expression of the Bcl2 oncoprotein and by the free oxygen radical scavenging enzyme Mn superoxide dismutase. Furthermore, in highly TNF-sensitive fibrosarcoma cells, antisense c-myc oligodeoxynucleotides caused a specific inhibition of TNF cytotoxicity. Our results suggest that the deregulation of c-Myc, which is common in human tumors and tumor cell lines is one reason why these cells are TNF sensitive.
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PMID:c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha. 795 10

The localization of Cu/Zn and Mn superoxide dismutase (SOD), which catalyzes the dismutation of superoxide radicals (O2-) to O2 and H2O2, in various thyroid disorders was studied by an immunohistochemical technique in 20% formalin fixed paraffin embedded thin sections using anti-human Cu/Zn and Mn-SOD antibodies. The concentrations of both SODs in those tissues were also measured by a sandwich enzyme immunoassay technique. Cu/Zn SOD was immunocytochemically stained in most of papillary carcinoma, and some of other disorders. In the normal follicular cells it localized in the perinuclear cytoplasm, whereas in the tumor or hyperplastic cells it was in the cytoplasm homogeneously. Mn SOD was strongly stained in papillary carcinoma and papillary growing cells in adenoma and Graves' disease. The concentrations of Cu/Zn and Mn SOD in every thyroid disorder were higher than those in normal thyroid, and it was much higher in the malignant tumors. The ratio of the concentration of Mn SOD against Cu/Zn SOD in the tissues was higher only in papillary carcinoma compared with that in normal thyroid. In conclusion, SOD seems to be relating to the cell proliferation and differentiation in the thyroid since both SODs increased in tumors and hyperplastic disorders, and Cu/Zn SOD changed its localization and Mn SOD existed predominantly in papillary carcinoma or papillary growing cells.
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PMID:[Study of the localization and the concentration of superoxide dismutase in various thyroid disorders]. 823 85

Manganese superoxide dismutase (MnSOD, encoded by the SOD2 gene mapping to chromosome 6q25) has been implicated as a tumor suppressor and as a metastasis suppressor in some tumor cell lines. We showed that introduction of an intact chromosome 6 into the metastatic melanoma cell line C8161 completely suppressed metastasis but did not affect tumorigenicity (Welch et al., (1994) Oncogene 9:255). The purpose of this study was to test whether SOD2 is the gene responsible for metastasis suppression. MnSOD protein levels of C8161 (measured by Western blot), before and after transfer of chromosome 6, showed no correlation with metastatic potential. To determine whether the lack of correlation was due to mutant, nonfunctional SOD2, a highly metastatic subclone of C8161 (C8161c1.9) was transfected with functional SOD2 or vector control (pSFFV). Metastatic potential and tumorigenicity were unchanged. Southern and Northern blots confirmed the presence of the transfected SOD2; however, total MnSOD protein and antioxidant activity were not significantly altered. These results suggest that levels of MnSOD are highly regulated within C8161 melanoma cells and that SOD2 does not suppress tumor formation nor metastatic potential in all human melanomas.
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PMID:SOD2 (MnSOD) does not suppress tumorigenicity or metastasis of human melanoma C8161 cells. 857 3

To determine whether non-hematologic tumors influence the bone marrow's antioxidant enzyme response to the radioprotective cytokine interleukin 1 alpha (IL-1), studies were undertaken using BDF1 and Balb/c mice bearing small, medium or large Lewis lung carcinoma (LLCa) or EMT6 mammary carcinoma tumors, respectively. Results demonstrated that, similar to nontumor-bearing mice, treatment of tumor-bearing animals with IL-1 was associated with a significant increase in marrow MnSOD activity. However, the duration of this elevated activity was reduced as tumor burden increased, and this reduction may have an impact on IL-1's ability to radioprotect tumor bearing animals, especially when tumor burden is large. In addition to cytokine-mediated responses, significant tumor-related influences on the marrow's antioxidant enzyme status were seen. Notably, it was observed that the presence of tumor was correlated with a marked suppression of antioxidant enzyme activity. Surprisingly, however, the pattern of enzyme suppression was found to differ between the two tumor models studied both in temporal onset and in the number of enzymes involved. In conclusion, the data obtained from these studies on tumor-bearing animals demonstrate that there are both cytokine-related and tumor-related influences which can effect the antioxidant enzyme status of the hematopoietic marrow-influences which may have the potential to alter the marrow's ability to tolerate free radical-generating events, both endogenous (i.e inflammation, infection) and exogenous (i.e. radiation, certain chemotherapeutic drugs) in origin.
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PMID:Antioxidant enzyme activity in murine hematopoietic bone marrow following treatment with interleukin 1 alpha: influence of tumor. 921 82

In an attempt to understand the change of superoxide dismutase (SOD) in tumor cells by hypoxia and hypoxia-normoxia exposure, the present study performed an in vitro investigation using rat glioma cell line in culture. Hypoxia was induced by an incubation with nitrogen gas for 15 h followed the normoxia exposure with air for 30 min. Activity of SOD in cytosolic and particulate of cells was determined by the reduction of nitroblue tetrazolium. Changes of mRNA for Cu,Zn-SOD or Mn-SOD were also characterized using Northern blotting analysis. Hypoxic stress decreased the activity of SOD, both Cu,Zn-SOD and Mn-SOD, in glioma cells. Expression of mRNA for SOD was elevated by hypoxic stress and the increase of mRNA level for Cu,Zn-SOD was more marked than that for Mn-SOD. In response to hypoxia-normoxia exposure, an increase of activity with a lower mRNA level for Mn-SOD was observed in glioma cells. However, changes of Cu,Zn-SOD both the activity and the level of mRNA were not found in glioma cells by hypoxia-normoxia. The obtained results suggest that the SOD in glioma cells can be activated to compensate the damage from free radicals during hypoxic stress.
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PMID:Changes of superoxide dismutase (SOD) mRNA and activity in response to hypoxic stress in cultured Wistar rat glioma cells. 930

Since response to radiation and markers capable of distinguishing metastatic from non-metastatic cells are important, we now use high-stringency mRNA differential display with immune blotting and protein-activity assays, to identify genes induced after exposure to UV in human metastatic C8161 melanoma and its counterpart neo 6.3, in which metastatic ability is suppressed by introduction of neo-tagged chromosome-6 fragments. We cloned and sequenced a 600-bp cDNA 99% homologous to Cu/Zn superoxide dismutase, which was up-regulated after UV irradiation in both metastatic variants, and showed increased basal expression at the mRNA, protein and activity levels in non-metastatic cells. The latter cells also showed greater basal activity of chromosome-6-associated MnSOD, slower proliferation and greater UV-mediated inducibility of the p53 tumor-suppressor protein than did its metastatic counterpart. Our data suggest that suppression of metastatic ability by introduction of neo-tagged chromosome-6 fragments promotes basal expression of superoxide dismutases and increases inducibility of p53 in response to DNA damage.
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PMID:Chromosome-6-mediated suppression of metastatic ability increases basal expression of UV-inducible superoxide dismutase and induction of p53. 967 63

Nitric oxide (NO) released from (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1,2-diolate (DETA/NO or NOC-18) induces apoptosis in human leukemia HL-60 cells. In this study, we isolated a HL-60 variant cell line, HL-NR6, that is resistant to DETA/NO toxicity as assessed by DNA fragmentation, morphology, and colony forming ability. The variant cells also showed resistance to reactive oxygen species (ROS) such as superoxide and hydrogen peroxide as well as NO donors, but not to anti-tumor drugs. We found that HL-NR6 cells when compared with HL-60 cells possessed twice the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase, but no change in Mn-SOD nor in glutathione peroxidase. Immunoblotting confirmed the high levels of both enzymes in the variant cell. We also observed that ROS generation following DETA/NO exposure was substantially higher in HL-60 cells than in HL-NR6 cells, using the 2',7'-dichlorofluorescein fluorometric method. Moreover, the SOD mimetic Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin and exogenous catalase effectively attenuated DETA/NO-elicited DNA fragmentation in HL-60 cells. Taken together, these data suggested that the NO resistance in HL-NR6 cells is associated with the increased Cu,Zn-SOD/catalase and that NO-mediated apoptosis in HL-60 cells is correlated with the generation of ROS and derived molecules like peroxynitrite.
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PMID:Resistance to nitric oxide-mediated apoptosis in HL-60 variant cells is associated with increased activities of Cu,Zn-superoxide dismutase and catalase. 989 23

To examine the role of reactive oxygen species on the invasive phenotype of cancer cells, we overexpressed manganese- and copper-zinc-containing superoxide dismutases (MnSOD, CuZnSOD) and catalase (Cat) in hamster cheek pouch carcinoma (HCPC-1) cells in vitro using adenoviral vector-mediated gene transfer. Hamster cheek pouch carcinoma cells were transduced with these adenoviral vector constructs alone, or in combination, at concentrations [i.e., multiplicity of infectivity (MOI)] of 100 MOI each. The Escherichia coli beta-galactosidase reporter construct was used as a control virus. Protein expression was examined by Western blot analysis and enzymatic activities were measured using spectrophotometry. To observe the effects of transgene overexpression on in vitro tumor cell invasion, we used the membrane invasion culture system, an accurate and reliable method for examining tumor cell invasion, in vitro. This assay measures the ability of tumor cells to invade a basement membrane matrix consisting of type IV collagen, laminin, and gelatin. MnSOD overexpression resulted in a 50% increase in HCPC-1 cell invasiveness (p < .001); co-overexpression of MnSOD with Cat partially inhibited this effect (p < .05). Moreover, co-overexpression of both SODs resulted in a significant increase in invasiveness compared with the parental HCPC-1 cells (p < .05). These changes could not be correlated with the 72 kDa collagenase IV or stromolysin activities using zymography, or the downregulation of the adhesion molecules E-cadherin or the alpha4 subunit of the alpha4beta1 integrin. These results suggest that hydrogen peroxide may play a role in the process of tumor cell invasion, but that the process does not rely on changes in matrix metalloproteinase activity in the cells, or the expression of cell adhesion molecules.
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PMID:Effects of antioxidant enzyme overexpression on the invasive phenotype of hamster cheek pouch carcinoma cells. 1049 Feb 77


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